Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Project description:BackgroundUndernutrition is one of the most common problems among people living with HIV, contributing to premature death and the development of comorbidities within this population. In Sub-Saharan Africa (SSA), the impacts of these often inter-related conditions appear in a series of fragmented and inconclusive studies. Thus, this review examines the pooled effects of undernutrition on mortality and morbidities among adults living with HIV in SSA.MethodsA systematic literature search was conducted from PubMed, EMBASE, CINAHL, and Scopus databases. All observational studies reporting the effects of undernutrition on mortality and morbidity among adults living with HIV in SSA were included. Heterogeneity between the included studies was assessed using the Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger's and Begg's tests at a 5% significance level. Finally, a random-effects meta-analysis model was employed to estimate the overall adjusted hazard ratio.ResultsOf 4309 identified studies, 53 articles met the inclusion criteria and were included in this review. Of these, 40 studies were available for the meta-analysis. A meta-analysis of 23 cohort studies indicated that undernutrition significantly (AHR: 2.1, 95% CI: 1.8, 2.4) increased the risk of mortality among adults living with HIV, while severely undernourished adults living with HIV were at higher risk of death (AHR: 2.3, 95% CI: 1.9, 2.8) as compared to mildly undernourished adults living with HIV. Furthermore, the pooled estimates of ten cohort studies revealed that undernutrition significantly increased the risk of developing tuberculosis (AHR: 2.1, 95% CI: 1.6, 2.7) among adults living with HIV.ConclusionThis review found that undernutrition has significant effects on mortality and morbidity among adults living with HIV. As the degree of undernutrition became more severe, mortality rate also increased. Therefore, findings from this review may be used to update the nutritional guidelines used for the management of PLHIV by different stakeholders, especially in limited-resource settings.

Project description:BackgroundIncomplete ascertainment of outcomes in randomized controlled trials (RCTs) is likely to bias final study results if reasons for unavailability of patient data are associated with the outcome of interest. The primary objective of this study is to assess the potential impact of loss to follow-up on the estimates of treatment effect. The secondary objectives are to describe, for published RCTs, (1) the reporting of loss to follow-up information, (2) the analytic methods used for handling loss to follow-up information, and (3) the extent of reported loss to follow-up.MethodsWe will conduct a systematic review of reports of RCTs recently published in five top general medical journals. Eligible RCTs will demonstrate statistically significant effect estimates with respect to primary outcomes that are patient-important and expressed as binary data. Teams of 2 reviewers will independently determine eligibility and extract relevant information from each eligible trial using standardized, pre-piloted forms. To assess the potential impact of loss to follow-up on the estimates of treatment effect we will, for varying assumptions about the outcomes of participants lost to follow-up (LTFU), calculate (1) the percentage of RCTs that lose statistical significance and (2) the mean change in effect estimate across RCTs. The different assumptions we will test are the following: (1) none of the LTFU participants had the event; (2) all LTFU participants had the event; (3) all LTFU participants in the treatment group had the event; none of those in the control group had it (worst case scenario); (4) the event incidence among LTFU participants (relative to observed participants) increased, with a higher relative increase in the intervention group; and (5) the event incidence among LTFU participants (relative to observed participants) increased in the intervention group and decreased in the control group.DiscussionWe aim to make our objectives and methods transparent. The results of this study may have important implications for both clinical trialists and users of the medical literature.

Project description:BackgroundGirl child marriage, a formal union of a female before age 18, and undernutrition remain common in Sub-Saharan Africa. The aim of this study is to establish the extent to which girl child marriage contributes to socioeconomic status and underweight, a measure of undernutrition, among adult women.MethodsWe used data from 103 Demographic and Health Surveys (DHS), representing 35 African countries from 1991 to 2014. Girl child marriage was coded both as a binary variable (before 18 years) and categorical variable (before 14, 14 to 15 years, 16 to 17 years). The primary outcome was underweight (body mass index less than 18·5). Secondary outcomes were early and multiple childbearing, secondary education completion, and wealth index. Logistic regression models were used to estimate associations.ResultsFifty-five percent of women married before age 18. Girl child marriage was associated with reduced risk of being underweight both in models adjusted for basic confounders (risk difference = - 0.020, 95% CI [- 0.026, - 0.014], p < 0.01) and in models adjusted for childbearing, women's relative status, and socioeconomic outcomes (risk difference = - 0.018, 95% CI [- 0.024, - 0.011], p < 0.01). Conditional on completing primary education and community fixed-effects, women married before 18 years had an increased risk of early motherhood (risk difference = 0.38, 95% CI [0.38, 0.38], p < 0.01) and of being in the poorest quintile (risk difference = 0.024, 95% CI [0.012, 0.036], p < 0.01), and were 27 percentage points less likely to complete secondary education (risk difference = - 0.27, 95% CI [- 0.28, - 0.26)], p < 001), compared to women married as adults.ConclusionsThough associated with substantially reduced socioeconomic status, girl child marriage appears to be associated with slightly reduced risk of being underweight in the population studied. Further research is needed to understand the determinants of undernutrition in this context as well as the broader relationship between socioeconomic status and nutritional outcomes.

Project description:BackgroundThe World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.Methods and findingsWe developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year.ConclusionsThe amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up.

Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects

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Does undernutrition increase the risk of lost to follow-up in adults living with HIV in sub-Saharan Africa? Protocol for a systematic review and meta-analysis.

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